[en] Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.
Disciplines :
Environmental sciences & ecology
Author, co-author :
Foreman, Amy L ; European Molecular Biology Laboratory & European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton CB10 1SD, U.K
Warth, Benedikt ; Department of Food Chemistry and Toxicology, University of Vienna, 1090 Vienna, Austria
Hessel, Ellen V S; National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands
Price, Elliott J; RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, Brno 60200, Czech Republic
Cantelli, Gaia; European Molecular Biology Laboratory & European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton CB10 1SD, U.K
Parkinson, Helen; European Molecular Biology Laboratory & European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton CB10 1SD, U.K
Hecht, Helge; RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, Brno 60200, Czech Republic
Klánová, Jana; RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, Brno 60200, Czech Republic
Vlaanderen, Jelle; Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Heidelberglaan 8 3584 CS Utrecht, The Netherlands
Hilscherova, Klara; RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, Brno 60200, Czech Republic
Vrijheid, Martine; Institute for Global Health (ISGlobal), Barcelona Biomedical Research Park (PRBB), Doctor Aiguader, 88, 08003 Barcelona, Spain ; Universitat Pompeu Fabra, Carrer de la Mercè, 12, Ciutat Vella, 08002 Barcelona, Spain ; Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Av. Monforte de Lemos, 3-5. Pebellón 11, Planta 0, 28029 Madrid, Spain
Vineis, Paolo ; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London SW7 2AZ, U.K
Araujo, Rita; European Commission, DG Research and Innovation, Sq. Frère-Orban 8, 1000 Bruxelles, Belgium
Barouki, Robert; Université Paris Cité, Inserm unit, 1124 Paris, France
Vermeulen, Roel ; Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Heidelberglaan 8 3584 CS Utrecht, The Netherlands
Lanone, Sophie; Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
Brunak, Søren; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Blegdamsvej 3B, 2200 København, Denmark
Sebert, Sylvain; Research Unit of Population Health, University of Oulu, P.O. Box 8000, FI-90014 Oulu, Finland
Karjalainen, Tuomo; European Commission, DG Research and Innovation, Sq. Frère-Orban 8, 1000 Bruxelles, Belgium
Institut National de la Sant? et de la Recherche M?dicale Fonds National de la Recherche Luxembourg Novo Nordisk Fonden European Molecular Biology Laboratory
Funding text :
Our vision is to develop a connected community of scientists who address exposome research questions through dynamic interdisciplinary collaborations across fields such as epidemiology, toxicology, public and environmental health, bioinformatics, and the biomedical and social sciences. The impacts would be enhanced by robust, scalable research infrastructure and funding opportunities that are responsive to the interdisciplinary, interconnected nature of exposome research. Moving away from classical single-exposure single-outcome approaches, research funding in the past decade has reflected the value of cross-cutting, integrative approaches to understand adverse or protective effects of multiple exposures over various life periods. These efforts build on current funding approaches headed by the European Commission, including the European Human Exposome Network (EHEN), a cluster of nine research and innovation action projects, and subsequent research infrastructure support through the European Strategy Forum on Research Infrastructures (ESFRI) to form the Environmental Exposure Assessment Research Infrastructure (EIRENE). This program of work has established the EU as a global leader in exposome research, further supported by the initiation of a Horizon Europe coordination and support action in 2024 to leverage an International Human Exposome Network (IHEN); this network will be linked with similar efforts in the US National Institutes of Health (NIH) call 2024 to promote and advance international cooperation in exposome science.The contents of this paper arose from a collaborative workshop run in 2020 on \u201CConnecting molecular biology and big data in humans to study the exposome\u201D funded and coordinated by the Human Ecosystems Transversal Theme (European Molecular Biology Laboratory) and Inserm with support provided by HP and GC. Thanks go to participants Ewan Birney, Remy Slama, Naomi Allen, Marc Chadeau, Andreas Kortenkamp, William Bourguet, Samuli Ripatti, Marc Chadeau-Hyam, and Xavier Basagan\u0301a. S.B. acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). E.L.S. acknowledges funding support from the Luxembourg National Research Fund (FNR) for project A18/BM/12341006. E.J.P., H.H., J.K., and K.H. acknowledge the research infrastructure RECETOX RI (LM2023069), H2020 CETOCOEN Excellence 857560, and OP RDE CZ.02.1.01/0.0/0.0/17_043/0009632. E.L.S. acknowledges funding support from the Luxembourg National Research Fund (FNR) for project A18/BM/12341006. This publication reflects only the authors\u2019 views, and the European Commission is not responsible for any use that may be made of the information it contains.
Wild, C. P. Complementing the Genome with an “Exposome”: The Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology. Cancer Epidemiology Biomarkers and Prevention 2005, 14, 1847- 1850, 10.1158/1055-9965.EPI-05-0456
Price, E. J.; Vitale, C. M.; Miller, G. W.; David, A.; Barouki, R.; Audouze, K.; Walker, D. I.; Antignac, J.-P.; Coumoul, X.; Bessonneau, V.; Klá Nová, J. Merging the Exposome into an Integrated Framework for “‘omics’” Sciences. iScience 2022, 25, 103976, 10.1016/j.isci.2022.103976
Miller, G. W.; Jones, D. P. The Nature of Nurture: Refining the Definition of the Exposome. Toxicol. Sci. 2014, 137 ( 1), 1- 2, 10.1093/toxsci/kft251
Peters, A.; Nawrot, T. S.; Baccarelli, A. A. Hallmarks of Environmental Insults. Cell. 2021, 184, 1455- 1468, 10.1016/j.cell.2021.01.043
Maitre, L.; Bustamante, M.; Hernández-Ferrer, C.; Thiel, D.; Lau, C. H. E.; Siskos, A. P.; Vives-Usano, M.; Ruiz-Arenas, C.; Pelegrí-Sisó, D.; Robinson, O.; Mason, D.; Wright, J.; Cadiou, S.; Slama, R.; Heude, B.; Casas, M.; Sunyer, J.; Papadopoulou, E. Z.; Gutzkow, K. B.; Andrusaityte, S.; Grazuleviciene, R.; Vafeiadi, M.; Chatzi, L.; Sakhi, A. K.; Thomsen, C.; Tamayo, I.; Nieuwenhuijsen, M.; Urquiza, J.; Borràs, E.; Sabidó, E.; Quintela, I.; Carracedo, Á.; Estivill, X.; Coen, M.; González, J. R.; Keun, H. C.; Vrijheid, M. Multi-Omics Signatures of the Human Early Life Exposome. Nat. Commun. 2022, 13 ( 1), 7024, 10.1038/s41467-022-34422-2
World Health Organization . The European Health Report 2021; World Health Organisation: 2021.
European Commission . Research and Innovation to Address the Impact of Environmental Factors on Health.; Publications Office of the European Union: 2022.
Vermeulen, R.; Schymanski, E. L.; Barabási, A. L.; Miller, G. W. The Exposome and Health: Where Chemistry Meets Biology. Science (1979) 2020, 367 ( 6476), 392- 396, 10.1126/science.aay3164
Vermeulen, R. Invited Perspective: Inroads to Biology-Informed Exposomics. Environ. Health Perspect 2022, 130 ( 11), 1, 10.1289/EHP12224
Zhang, P.; Chen, P. L.; Li, Z. H.; Zhang, A.; Zhang, X. R.; Zhang, Y. J.; Liu, D.; Mao, C. Association of Smoking and Polygenic Risk with the Incidence of Lung Cancer: A Prospective Cohort Study. British Journal of Cancer 2022 126:11 2022, 126 ( 11), 1637- 1646, 10.1038/s41416-022-01736-3
Zhang, P.; Carlsten, C.; Chaleckis, R.; Hanhineva, K.; Huang, M.; Isobe, T.; Koistinen, V. M.; Meister, I.; Papazian, S.; Sdougkou, K.; Xie, H.; Martin, J. W.; Rappaport, S. M.; Tsugawa, H.; Walker, D. I.; Woodruff, T. J.; Wright, R. O.; Wheelock, C. E. Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective. Environmental Science and Technology Letters 2021, 8, 839- 852, 10.1021/acs.estlett.1c00648
Ohanyan, H.; Portengen, L.; Kaplani, O.; Huss, A.; Hoek, G.; Beulens, J. W. J.; Lakerveld, J.; Vermeulen, R. Associations between the Urban Exposome and Type 2 Diabetes: Results from Penalised Regression by Least Absolute Shrinkage and Selection Operator and Random Forest Models. Environ. Int. 2022, 170, 107592, 10.1016/j.envint.2022.107592
Brun-Usan, M.; Zimm, R.; Uller, T. Beyond Genotype-Phenotype Maps: Toward a Phenotype-Centered Perspective on Evolution. BioEssays 2022, 44 ( 9), 2100225, 10.1002/bies.202100225
Xue, B. K.; Sartori, P.; Leibler, S. Environment-to-Phenotype Mapping and Adaptation Strategies in Varying Environments. Proc. Natl. Acad. Sci. U. S. A. 2019, 116 ( 28), 13847- 13855, 10.1073/pnas.1903232116
Gudi-Mindermann, H.; White, M.; Roczen, J.; Riedel, N.; Dreger, S.; Bolte, G. Integrating the Social Environment with an Equity Perspective into the Exposome Paradigm: A New Conceptual Framework of the Social Exposome. Environ. Res. 2023, 233, 116485, 10.1016/j.envres.2023.116485
Tarazona, S.; Arzalluz-Luque, A.; Conesa, A. Undisclosed, Unmet and Neglected Challenges in Multi-Omics Studies. Nature Computational Science 2021, 1, 395- 402, 10.1038/s43588-021-00086-z
Adrian-Kalchhauser, I.; Sultan, S. E.; Shama, L. N. S.; Spence-Jones, H.; Tiso, S.; Keller Valsecchi, C. I.; Weissing, F. J. Understanding “Non-Genetic” Inheritance: Insights from Molecular-Evolutionary Crosstalk. Trends in Ecology and Evolution 2020, 35, 1078- 1089, 10.1016/j.tree.2020.08.011
Macartney, E. L.; Drobniak, S. M.; Nakagawa, S.; Lagisz, M. Non-Genetic Inheritance of Environmental Exposures: A Protocol for a Map of Systematic Reviews with Bibliometric Analysis. Environ. Evid 2021, 10 ( 1), 31, 10.1186/s13750-021-00245-9
Hanson, M. A.; Poston, L.; Gluckman, P. D. DOHaD - The Challenge of Translating the Science to Policy. Journal of Developmental Origins of Health and Disease 2019, 10, 263- 267, 10.1017/S2040174419000205
Vineis, P.; Barouki, R. The Exposome as the Science of Social-to-Biological Transitions. Environ. Int. 2022, 165, 107312, 10.1016/j.envint.2022.107312
Phelan, J. C.; Link, B. G.; Tehranifar, P. Social Conditions as Fundamental Causes of Health Inequalities: Theory, Evidence, and Policy Implications. J. Health Soc. Behav 2010, 51, S28- S40, 10.1177/0022146510383498
Forde, A. T.; Crookes, D. M.; Suglia, S. F.; Demmer, R. T. Weathering Hypothesis as an Explanation for Racial Disparities in Health: A Systematic Review 2019, 33, 1, 10.1016/j.annepidem.2019.02.011
ADR UK . ADR UK Annual Report; 2021.
Aurich, D.; Miles, O.; Schymanski, E. L. Historical Exposomics and High Resolution Mass Spectrometry. Exposome 2021, 1, 1, 10.1093/exposome/osab007
Linkov, I.; Loney, D.; Cormier, S.; Satterstrom, F. K.; Bridges, T. Weight-of-Evidence Evaluation in Environmental Assessment: Review of Qualitative and Quantitative Approaches. Science of The Total Environment 2009, 407 ( 19), 5199- 5205, 10.1016/j.scitotenv.2009.05.004
Wu, Y.; Hoffman, F. O.; Apostoaei, A. I.; Kwon, D.; Thomas, B. A.; Glass, R.; Zablotska, L. B. Methods to Account for Uncertainties in Exposure Assessment in Studies of Environmental Exposures. Environ. Health 2019, 18 ( 1), 1- 15, 10.1186/s12940-019-0468-4
O’Cathain, A.; Murphy, E.; Nicholl, J. Three Techniques for Integrating Data in Mixed Methods Studies. BMJ. 2010, 341, c4587, 10.1136/BMJ.C4587
Ding, Y.; Hou, K.; Xu, Z.; Pimplaskar, A.; Petter, E.; Boulier, K.; Privé, F.; Vilhjálmsson, B. J.; Olde Loohuis, L. M.; Pasaniuc, B. Polygenic Scoring Accuracy Varies across the Genetic Ancestry Continuum. Nature 2023, 618 ( 7966), 774- 781, 10.1038/s41586-023-06079-4
Patel, A. P.; Wang, M.; Ruan, Y.; Koyama, S.; Clarke, S. L.; Yang, X.; Tcheandjieu, C.; Agrawal, S.; Fahed, A. C.; Ellinor, P. T.; Tsao, P. S.; Sun, Y. V.; Cho, K.; Wilson, P. W. F.; Assimes, T. L.; van Heel, D. A.; Butterworth, A. S.; Aragam, K. G.; Natarajan, P.; Khera, A. V. A Multi-Ancestry Polygenic Risk Score Improves Risk Prediction for Coronary Artery Disease. Nature Medicine 2023 29:7 2023, 29 ( 7), 1793- 1803, 10.1038/s41591-023-02429-x
Castagné, R.; Ménard, S.; Delpierre, C. The Epigenome as a Biological Candidate to Incorporate the Social Environment over the Life Course and Generations. Epigenomics 2023, 15 ( 1), 5- 10, 10.2217/epi-2022-0457
Barouki, R.; Melén, E.; Herceg, Z.; Beckers, J.; Chen, J.; Karagas, M.; Puga, A.; Xia, Y.; Chadwick, L.; Yan, W.; Audouze, K.; Slama, R.; Heindel, J.; Grandjean, P.; Kawamoto, T.; Nohara, K. Epigenetics as a Mechanism Linking Developmental Exposures to Long-Term Toxicity. Environ. Int. 2018, 114, 77- 86, 10.1016/j.envint.2018.02.014
McCrory, C.; Fiorito, G.; Ni Cheallaigh, C.; Polidoro, S.; Karisola, P.; Alenius, H.; Layte, R.; Seeman, T.; Vineis, P.; Kenny, R. A. How Does Socio-Economic Position (SEP) Get Biologically Embedded? A Comparison of Allostatic Load and the Epigenetic Clock(s). Psychoneuroendocrinology 2019, 104, 64- 73, 10.1016/j.psyneuen.2019.02.018
Chadeau-Hyam, M.; Bodinier, B.; Vermeulen, R.; Karimi, M.; Zuber, V.; Castagné, R.; Elliott, J.; Muller, D.; Petrovic, D.; Whitaker, M.; Stringhini, S.; Tzoulaki, I.; Kivimäki, M.; Vineis, P.; Elliott, P.; Kelly-Irving, M.; Delpierre, C. Education, Biological Ageing, All-Cause and Cause-Specific Mortality and Morbidity: UK Biobank Cohort Study. EClinicalMedicine 2020, 29-30, 100658, 10.1016/j.eclinm.2020.100658
Fiorito, G.; McCrory, C.; Robinson, O.; Carmeli, C.; Rosales, C. O.; Zhang, Y.; Colicino, E.; Dugue, P.-A.; Artaud, F.; McKay, G. J; Jeong, A.; Mishra, P. P; Nøst, T. H; Krogh, V.; Panico, S.; Sacerdote, C.; Tumino, R.; Palli, D.; Matullo, G.; Guarrera, S.; Gandini, M.; Bochud, M.; Dermitzakis, E.; Muka, T.; Schwartz, J.; Vokonas, P. S; Just, A.; Hodge, A. M; Giles, G. G; Southey, M. C; Hurme, M. A; Young, I.; McKnight, A. J.; Kunze, S.; Waldenberger, M.; Peters, A.; Schwettmann, L.; Lund, E.; Baccarelli, A.; Milne, R. L; Kenny, R. A; Elbaz, A.; Brenner, H.; Kee, F.; Voortman, T.; Probst-Hensch, N.; Lehtimaki, T.; Elliot, P.; Stringhini, S.; Vineis, P.; Polidoro, S. Socioeconimic Position, Lifestyle Habits and Biomarkers of Epigenetic Aging: A Multi-Cohort Analysis. Aging 2019, 11 ( 7), 2045, 10.18632/aging.101900
Gravlee, C. C. How Race Becomes Biology: Embodiment of Social Inequality. Am. J. Phys. Anthropol 2009, 139 ( 1), 47- 57, 10.1002/ajpa.20983
Neufcourt, L.; Castagné, R.; Mabile, L.; Khalatbari-Soltani, S.; Delpierre, C.; Kelly-Irving, M. Assessing How Social Exposures Are Integrated in Exposome Research: A Scoping Review. Environ. Health Perspect 2022, 130 ( 11), 116001, 10.1289/EHP11015
McCrory, C.; Fiorito, G.; McLoughlin, S.; Polidoro, S.; Cheallaigh, C. N.; Bourke, N.; Karisola, P.; Alenius, H.; Vineis, P.; Layte, R.; Kenny, R. A. Epigenetic Clocks and Allostatic Load Reveal Potential Sex-Specific Drivers of Biological Aging. Journals of Gerontology - Series A Biological Sciences and Medical Sciences 2019, 75 ( 3), 495- 503, 10.1093/gerona/glz241
UK Biobank . UK BioBank Releases. www.ukbiobank.ac.uk.
Ayeni, K. I.; Berry, D.; Wisgrill, L.; Warth, B.; Ezekiel, C. N. Early-Life Chemical Exposome and Gut Microbiome Development: African Research Perspectives within a Global Environmental Health Context. Trends in Microbiology 2022, 1084- 1100, 10.1016/j.tim.2022.05.008
Huang, Y.; Fang, M. Nutritional and Environmental Contaminant Exposure: A Tale of Two Co-Existing Factors for Disease Risks. Environ. Sci. Technol. 2020, 54 ( 23), 14793- 14796, 10.1021/acs.est.0c05658
Van Breda, S. G. J.; Wilms, L. C.; Gaj, S.; Jennen, D. G. J.; Briedé, J. J.; Kleinjans, J. C. S.; De Kok, T. M. C. M. The Exposome Concept in a Human Nutrigenomics Study: Evaluating the Impact of Exposure to a Complex Mixture of Phytochemicals Using Transcriptomics Signatures. Mutagenesis 2015, 30 ( 6), 723- 731, 10.1093/mutage/gev008
Noerman, S.; Kokla, M.; Koistinen, V. M.; Lehtonen, M.; Tuomainen, T. P.; Brunius, C.; Virtanen, J. K.; Hanhineva, K. Associations of the Serum Metabolite Profile with a Healthy Nordic Diet and Risk of Coronary Artery Disease. Clin Nutr 2021, 40 ( 5), 3250- 3262, 10.1016/j.clnu.2020.10.051
Noerman, S.; Kokla, M.; Koistinen, V. M.; Lehtonen, M.; Tuomainen, T. P.; Brunius, C.; Virtanen, J. K.; Hanhineva, K. Associations of the Serum Metabolite Profile with a Healthy Nordic Diet and Risk of Coronary Artery Disease. Clin Nutr 2021, 40 ( 5), 3250- 3262, 10.1016/j.clnu.2020.10.051
Gil, A. M.; Duarte, D.; Pinto, J.; Barros, A. S. Assessing Exposome Effects on Pregnancy through Urine Metabolomics of a Portuguese (Estarreja) Cohort. J. Proteome Res. 2018, 17 ( 3), 1278- 1289, 10.1021/acs.jproteome.7b00878
González-Domínguez, R.; Jáuregui, O.; Queipo-Ortuño, M. I.; Andrés-Lacueva, C. Characterization of the Human Exposome by a Comprehensive and Quantitative Large-Scale Multianalyte Metabolomics Platform. Anal. Chem. 2020, 92 ( 20), 13767- 13775, 10.1021/acs.analchem.0c02008
Petrick, L. M.; Uppal, K.; Funk, W. E. Metabolomics and Adductomics of Newborn Bloodspots to Retrospectively Assess the Early-Life Exposome. Curr. Opin Pediatr 2020, 32 ( 2), 300, 10.1097/MOP.0000000000000875
Warth, B.; Spangler, S.; Fang, M.; Johnson, C. H.; Forsberg, E. M.; Granados, A.; Martin, R. L.; Domingo-Almenara, X.; Huan, T.; Rinehart, D.; Montenegro-Burke, J. R.; Hilmers, B.; Aisporna, A.; Hoang, L. T.; Uritboonthai, W.; Benton, H. P.; Richardson, S. D.; Williams, A. J.; Siuzdak, G. Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing. Anal. Chem. 2017, 89 ( 21), 11505- 11513, 10.1021/acs.analchem.7b02759
Flasch, M.; Fitz, V.; Rampler, E.; Ezekiel, C. N.; Koellensperger, G.; Warth, B. Integrated Exposomics/Metabolomics for Rapid Exposure and Effect Analyses. JACS Au 2022, 2 ( 11), 2548- 2560, 10.1021/jacsau.2c00433
Mazur, D. M.; Detenchuk, E. A.; Sosnova, A. A.; Artaev, V. B.; Lebedev, A. T. GC-HRMS with Complimentary Ionization Techniques for Target and Non-Target Screening for Chemical Exposure: Expanding the Insights of the Air Pollution Markers in Moscow Snow. Sci. Total Environ. 2021, 144506, 10.1016/j.scitotenv.2020.144506
Escher, B. I.; Stapleton, H. M.; Schymanski, E. L. Tracking Complex Mixtures of Chemicals in Our Changing Environment. Science 2020, 367 ( 6476), 388, 10.1126/science.aay6636
Jamnik, T.; Flasch, M.; Braun, D.; Fareed, Y.; Wasinger, D.; Seki, D.; Berry, D.; Berger, A.; Wisgrill, L.; Warth, B. Next-Generation Biomonitoring of the Early-Life Chemical Exposome in Neonatal and Infant Development. Nature Communications 2022 13:1 2022, 13 ( 1), 1- 14, 10.1038/s41467-022-30204-y
Hollender, J.; Schymanski, E. L.; Singer, H. P.; Ferguson, P. L. Nontarget Screening with High Resolution Mass Spectrometry in the Environment: Ready to Go?. Environ. Sci. Technol. 2017, 51 ( 20), 11505- 11512, 10.1021/acs.est.7b02184
Boyce, W. T.; Sokolowski, M. B.; Robinson, G. E. Genes and Environments, Development and Time. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 ( 38), 23235- 23241, 10.1073/pnas.2016710117
Winsvold, B. S.; Harder, A. V. E.; Ran, C.; Chalmer, M. A.; Dalmasso, M. C.; Ferkingstad, E.; Tripathi, K. P.; Bacchelli, E.; Børte, S.; Fourier, C.; Petersen, A. S.; Vijfhuizen, L. S.; Magnusson, S. H.; O’Connor, E.; Bjornsdottir, G.; Häppölä, P.; Wang, Y. F.; Callesen, I.; Kelderman, T.; Gallardo, V. J.; de Boer, I.; Olofsgård, F. J.; Heinze, K.; Lund, N.; Thomas, L. F.; Hsu, C. L.; Pirinen, M.; Hautakangas, H.; Ribasés, M.; Guerzoni, S.; Sivakumar, P.; Yip, J.; Heinze, A.; Küçükali, F.; Ostrowski, S. R.; Pedersen, O. B.; Kristoffersen, E. S.; Martinsen, A. E.; Artigas, M. S.; Lagrata, S.; Cainazzo, M. M.; Adebimpe, J.; Quinn, O.; Göbel, C.; Cirkel, A.; Volk, A. E.; Heilmann-Heimbach, S.; Skogholt, A. H.; Gabrielsen, M. E.; Wilbrink, L. A.; Danno, D.; Mehta, D.; Guobjartsson, D. F.; Rosendaal, F. R.; Willems van Dijk, K.; Fronczek, R.; Wagner, M.; Scherer, M.; Göbel, H.; Sleegers, K.; Sveinsson, O. A.; Pani, L.; Zoli, M.; Ramos-Quiroga, J. A.; Dardiotis, E.; Steinberg, A.; Riedel-Heller, S.; Sjöstrand, C.; Thorgeirsson, T. E.; Stefansson, H.; Southgate, L.; Trembath, R. C.; Vandrovcova, J.; Noordam, R.; Paemeleire, K.; Stefansson, K.; Fann, C. S. J.; Waldenlind, E.; Tronvik, E.; Jensen, R. H.; Chen, S. P.; Houlden, H.; Terwindt, G. M.; Kubisch, C.; Maestrini, E.; Vikelis, M.; Pozo-Rosich, P.; Belin, A. C.; Matharu, M.; van den Maagdenberg, A. M. J. M.; Hansen, T. F.; Ramirez, A.; Zwart, J. A. Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor. Ann. Neurol. 2023, 94 ( 4), 713- 726, 10.1002/ana.26743
Jiang, C.; Wang, X.; Li, X.; Inlora, J.; Wang, T.; Liu, Q.; Snyder, M. Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring. Cell 2018, 175 ( 1), 277- 291.e31, 10.1016/J.CELL.2018.08.060
Demetriou, C.; Vineis, P. Biomarkers and Omics of Health Effects Associated with Traffic-Related Air Pollution. Traffic-Related Air Pollution 2020, 281- 309, 10.1016/B978-0-12-818122-5.00011-9
Dennis, K. K.; Auerbach, S. S.; Balshaw, D. M.; Cui, Y.; Fallin, M. D.; Smith, M. T.; Spira, A.; Sumner, S.; Miller, G. W. The Importance of the Biological Impact of Exposure to the Concept of the Exposome. Environ. Health Perspect 2016, 124 ( 10), 1504, 10.1289/EHP140
Allesøe, R. L.; Lundgaard, A. T.; Hernández Medina, R.; Aguayo-Orozco, A.; Johansen, J.; Nissen, J. N.; Brorsson, C.; Mazzoni, G.; Niu, L.; Biel, J. H.; Brasas, V.; Webel, H.; Benros, M. E.; Pedersen, A. G.; Chmura, P. J.; Jacobsen, U. P.; Mari, A.; Koivula, R.; Mahajan, A.; Vinuela, A.; Tajes, J. F.; Sharma, S.; Haid, M.; Hong, M. G.; Musholt, P. B.; De Masi, F.; Vogt, J.; Pedersen, H. K.; Gudmundsdottir, V.; Jones, A.; Kennedy, G.; Bell, J.; Thomas, E. L.; Frost, G.; Thomsen, H.; Hansen, E.; Hansen, T. H.; Vestergaard, H.; Muilwijk, M.; Blom, M. T.; ‘t Hart, L. M.; Pattou, F.; Raverdy, V.; Brage, S.; Kokkola, T.; Heggie, A.; McEvoy, D.; Mourby, M.; Kaye, J.; Hattersley, A.; McDonald, T.; Ridderstråle, M.; Walker, M.; Forgie, I.; Giordano, G. N.; Pavo, I.; Ruetten, H.; Pedersen, O.; Hansen, T.; Dermitzakis, E.; Franks, P. W.; Schwenk, J. M.; Adamski, J.; McCarthy, M. I.; Pearson, E.; Banasik, K.; Rasmussen, S.; Brunak, S.; Froguel, P.; Thomas, C. E.; Haussler, R.; Beulens, J.; Rutters, F.; Nijpels, G.; van Oort, S.; Groeneveld, L.; Elders, P.; Giorgino, T.; Rodriquez, M.; Nice, R.; Perry, M.; Bianzano, S.; Graefe-Mody, U.; Hennige, A.; Grempler, R.; Baum, P.; Stærfeldt, H. H.; Shah, N.; Teare, H.; Ehrhardt, B.; Tillner, J.; Dings, C.; Lehr, T.; Scherer, N.; Sihinevich, I.; Cabrelli, L.; Loftus, H.; Bizzotto, R.; Tura, A.; Dekkers, K.; van Leeuwen, N.; Groop, L.; Slieker, R.; Ramisch, A.; Jennison, C.; McVittie, I.; Frau, F.; Steckel-Hamann, B.; Adragni, K.; Thomas, M.; Pasdar, N. A.; Fitipaldi, H.; Kurbasic, A.; Mutie, P.; Pomares-Millan, H.; Bonnefond, A.; Canouil, M.; Caiazzo, R.; Verkindt, H.; Holl, R.; Kuulasmaa, T.; Deshmukh, H.; Cederberg, H.; Laakso, M.; Vangipurapu, J.; Dale, M.; Thorand, B.; Nicolay, C.; Fritsche, A.; Hill, A.; Hudson, M.; Thorne, C.; Allin, K.; Arumugam, M.; Jonsson, A.; Engelbrechtsen, L.; Forman, A.; Dutta, A.; Sondertoft, N.; Fan, Y.; Gough, S.; Robertson, N.; McRobert, N.; Wesolowska-Andersen, A.; Brown, A.; Davtian, D.; Dawed, A.; Donnelly, L.; Palmer, C.; White, M.; Ferrer, J.; Whitcher, B.; Artati, A.; Prehn, C.; Adam, J.; Grallert, H.; Gupta, R.; Sackett, P. W.; Nilsson, B.; Tsirigos, K.; Eriksen, R.; Jablonka, B.; Uhlen, M.; Gassenhuber, J.; Baltauss, T.; de Preville, N.; Klintenberg, M.; Abdalla, M. Discovery of Drug-Omics Associations in Type 2 Diabetes with Generative Deep-Learning Models. Nat. Biotechnol. 2023, 41 ( 3), 399- 408, 10.1038/s41587-022-01520-x
Julkunen, H.; Cichońska, A.; Tiainen, M.; Koskela, H.; Nybo, K.; Mäkelä, V.; Nokso-Koivisto, J.; Kristiansson, K.; Perola, M.; Salomaa, V.; Jousilahti, P.; Lundqvist, A.; Kangas, A. J.; Soininen, P.; Barrett, J. C.; Würtz, P. Atlas of Plasma NMR Biomarkers for Health and Disease in 118,461 Individuals from the UK Biobank. Nat. Commun. 2023, 14 ( 1), 604, 10.1038/s41467-023-36231-7
deCode genetics. https://www.decode.com/.
Univesity of Helsinki . FINNGEN. https://www.finngen.fi/fi.
Osler, M.; Andersen, A. M. N.; Lund, R.; Batty, G. D.; Hougaard, C. Ø.; Damsgaard, M. T.; Due, P.; Holstein, B. E. Revitalising the Metropolit 1953 Danish Male Birth Cohort: Background, Aims and Design. Paediatr Perinat Epidemiol 2004, 18 ( 5), 385- 394, 10.1111/j.1365-3016.2004.00584.x
Uffelmann, E.; Huang, Q. Q.; Munung, N. S.; de Vries, J.; Okada, Y.; Martin, A. R.; Martin, H. C.; Lappalainen, T.; Posthuma, D. Genome-Wide Association Studies. Nature Reviews Methods Primers 2021, 59, 10.1038/s43586-021-00056-9
Diogo, D.; Tian, C.; Franklin, C. S.; Alanne-Kinnunen, M.; March, M.; Spencer, C. C. A.; Vangjeli, C.; Weale, M. E.; Mattsson, H.; Kilpeläinen, E.; Sleiman, P. M. A.; Reilly, D. F.; McElwee, J.; Maranville, J. C.; Chatterjee, A. K.; Bhandari, A.; Nguyen, K. D. H.; Estrada, K.; Reeve, M. P.; Hutz, J.; Bing, N.; John, S.; MacArthur, D. G.; Salomaa, V.; Ripatti, S.; Hakonarson, H.; Daly, M. J.; Palotie, A.; Hinds, D. A.; Donnelly, P.; Fox, C. S.; Day-Williams, A. G.; Plenge, R. M.; Runz, H. Phenome-Wide Association Studies across Large Population Cohorts Support Drug Target Validation. Nat. Commun. 2018, 9 ( 1), 4285, 10.1038/s41467-018-06540-3
Huang, S. Y.; Yang, Y. X.; Chen, S. D.; Li, H. Q.; Zhang, X. Q.; Kuo, K.; Tan, L.; Feng, L.; Dong, Q.; Zhang, C.; Yu, J. T. Investigating Causal Relationships between Exposome and Human Longevity: A Mendelian Randomization Analysis. BMC Med. 2021, 19 ( 1), 1- 16, 10.1186/s12916-021-02030-4
Currant, H.; Fitzgerald, T. W.; Patel, P. J.; Khawaja, A. P.; Webster, A. R.; Mahroo, O. A.; Birney, E. Sub-Cellular Level Resolution of Common Genetic Variation in the Photoreceptor Layer Identifies Continuum between Rare Disease and Common Variation. PLoS Genet 2023, 19 ( 2), e1010587, 10.1371/journal.pgen.1010587
McGurk, K. A.; Zhang, X.; Theotokis, P.; Thomson, K.; Buchan, R. J.; Mazaika, E.; Ormondroyd, E.; Macaya, D.; Jian Pua, C.; Funke, B.; MacArthur, D. G.; Prasad, S.; Cook, S. A.; Allouba, M.; Aguib, Y.; O, D. P.; R Barton, P. J.; Watkins, H.; Ware, J. S. The Penetrance of Rare Variants in Cardiomyopathy-Associated Genes: 1 a Cross-Sectional Approach to Estimate Penetrance for Secondary Findings 2. American Journal of Human Genetics 2023, 110, 1482, 10.1016/j.ajhg.2023.08.003
Alexandrov, L. B.; Kim, J.; Haradhvala, N. J.; Huang, M. N.; Wei, A.; Ng, T.; Wu, Y.; Boot, A.; Covington, K. R.; Gordenin, D. A.; Bergstrom, E. N.; Islam, S. M. A.; Lopez-Bigas, N.; Klimczak, L. J.; Mcpherson, J. R. The Repertoire of Mutational Signatures in Human Cancer. PCAWG Mutational Signatures Working Group 1943, 578, 15
Lambert, J. T.; Su-Feher, L.; Cichewicz, K.; Warren, T. L.; Zdilar, I.; Wang, Y.; Lim, K. J.; Haigh, J. L.; Morse, S. J.; Canales, C. P.; Stradleigh, T. W.; Palacios, E. C.; Haghani, V.; Moss, S. D.; Parolini, H.; Quintero, D.; Shrestha, D.; Vogt, D.; Byrne, L. C.; Nord, A. S. Parallel Functional Testing Identifies Enhancers Active in Early Postnatal Mouse Brain. eLife 2021, 10, 69479, 10.7554/eLife.69479
Wang, Y.; Namba, S.; Lopera, E.; Kerminen, S.; Tsuo, K.; Läll, K.; Kanai, M.; Zhou, W.; Wu, K. H.; Favé, M. J.; Bhatta, L.; Awadalla, P.; Brumpton, B.; Deelen, P.; Hveem, K.; Lo Faro, V.; Mägi, R.; Murakami, Y.; Sanna, S.; Smoller, J. W.; Uzunovic, J.; Wolford, B. N.; Wu, K. H. H.; Rasheed, H.; Hirbo, J. B.; Bhattacharya, A.; Zhao, H.; Surakka, I.; Lopera-Maya, E. A.; Chapman, S. B.; Karjalainen, J.; Kurki, M.; Mutaamba, M.; Partanen, J. J.; Chavan, S.; Chen, T. T.; Daya, M.; Ding, Y.; Feng, Y. C. A.; Gignoux, C. R.; Graham, S. E.; Hornsby, W. E.; Ingold, N.; Johnson, R.; Laisk, T.; Lin, K.; Lv, J.; Millwood, I. Y.; Palta, P.; Pandit, A.; Preuss, M. H.; Thorsteinsdottir, U.; Zawistowski, M.; Zhong, X.; Campbell, A.; Crooks, K.; de Bock, G. H.; Douville, N. J.; Finer, S.; Fritsche, L. G.; Griffiths, C. J.; Guo, Y.; Hunt, K. A.; Konuma, T.; Marioni, R. E.; Nomdo, J.; Patil, S.; Rafaels, N.; Richmond, A.; Shortt, J. A.; Straub, P.; Tao, R.; Vanderwerff, B.; Barnes, K. C.; Boezen, M.; Chen, Z.; Chen, C. Y.; Cho, J.; Smith, G. D.; Finucane, H. K.; Franke, L.; Gamazon, E. R.; Ganna, A.; Gaunt, T. R.; Ge, T.; Huang, H.; Huffman, J.; Koskela, J. T.; Lajonchere, C.; Law, M. H.; Li, L.; Lindgren, C. M.; Loos, R. J. F.; MacGregor, S.; Matsuda, K.; Olsen, C. M.; Porteous, D. J.; Shavit, J. A.; Snieder, H.; Trembath, R. C.; Vonk, J. M.; Whiteman, D.; Wicks, S. J.; Wijmenga, C.; Wright, J.; Zheng, J.; Zhou, X.; Boehnke, M.; Cox, N. J.; Geschwind, D. H.; Hayward, C.; Kenny, E. E.; Lin, Y. F.; Martin, H. C.; Medland, S. E.; Okada, Y.; Palotie, A. V.; Pasaniuc, B.; Stefansson, K.; van Heel, D. A.; Walters, R. G.; Zöllner, S.; Martin, A. R.; Willer, C. J.; Daly, M. J.; Neale, B. M.; Willer, C.; Hirbo, J. Global Biobank Analyses Provide Lessons for Developing Polygenic Risk Scores across Diverse Cohorts. Cell Genomics 2023, 3 ( 1), 100241, 10.1016/j.xgen.2022.100241
Sud, A.; Horton, R. H.; Hingorani, A. D.; Tzoulaki, I.; Turnbull, C.; Houlston, R. S.; Lucassen, A. Realistic Expectations Are Key to Realising the Benefits of Polygenic Scores. BMJ. 2023, 380, e073149, 10.1136/bmj-2022-073149
Araújo, D. S.; Wheeler, H. E. Genetic and Environmental Variation Impact Transferability of Polygenic Risk Scores. Cell Reports Medicine 2022, 3, 100687, 10.1016/j.xcrm.2022.100687
Wald, N. J.; Old, R. The Illusion of Polygenic Disease Risk Prediction. Genetics in Medicine 2019, 21 ( 8), 1705- 1707, 10.1038/s41436
Kang, J. B.; Raveane, A.; Nathan, A.; Soranzo, N.; Raychaudhuri, S. Methods and Insights from Single-Cell Expression Quantitative Trait Loci. Annu. Rev. Genom. Hum. Genet. 2023, 24, 277, 10.1146/annurev-genom-101422-100437
Rowland, B.; Venkatesh, S.; Tardaguila, M.; Wen, J.; Rosen, J. D.; Tapia, A. L.; Sun, Q.; Graff, M.; Vuckovic, D.; Lettre, G.; Sankaran, V. G.; Voloudakis, G.; Roussos, P.; Huffman, J. E.; Reiner, A. P.; Soranzo, N.; Raffield, L. M.; Li, Y. Transcriptome-Wide Association Study in UK Biobank Europeans Identifies Associations with Blood Cell Traits. Hum. Mol. Genet. 2022, 31, 2333- 2347, 10.1093/hmg/ddac011
He, H.; He, M. M.; Wang, H.; Qiu, W.; Liu, L.; Long, L.; Shen, Q.; Zhang, S.; Qin, S.; Lu, Z.; Cai, Y.; Zhang, M.; Niu, S.; Li, J.; Shen, N.; Zhu, Y.; Tian, J.; Chang, J.; Miao, X.; Zhong, R. In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood. Am. J. Respir Crit Care Med. 2023, 207 ( 2), 173- 182, 10.1164/rccm.202112-2758OC
Kocsmár, É.; Buzás, G. M.; Szirtes, I.; Kocsmár, I.; Kramer, Z.; Szijártó, A.; Fadgyas-Freyler, P.; Szénás, K.; Rugge, M.; Fassan, M.; Kiss, A.; Schaff, Z.; Röst, G.; Lotz, G. Primary and Secondary Clarithromycin Resistance in Helicobacter Pylori and Mathematical Modeling of the Role of Macrolides. Nat. Commun. 2021, 12 ( 1), 2255, 10.1038/s41467-021-22557-7
Aguayo-Orozco, A.; Haue, A. D.; Jørgensen, I. F.; Westergaard, D.; Moseley, P. L.; Mortensen, L. H.; Brunak, S. Optimizing Drug Selection from a Prescription Trajectory of One Patient. NPJ. Digit Med. 2021, 4 ( 1), 150, 10.1038/s41746-021-00522-4
Christensen, D. M.; Gislason, G.; Gerds, T. Matters Arising: Immortal Time Bias in the Analysis of Drug Prescription Trajectories. NPJ. Digit Med. 2022, 5, 190, 10.1038/s41746-021-00522-4
Thier, R.; Bruning, T.; Roos, P. H.; Rihs, H.-P.; Golka, K.; Ko, Y.; Bolt, H. M. Markers of Genetic Susceptibility in Human Environmental Hygiene and Toxicology: The Role of Selected CYP, NAT and GST Genes. Int. J. Hyg. Environ. Health 2003, 206, 149- 171, 10.1078/1438-4639-00209
Carlini, V.; Policarpi, C.; Hackett, J. A. Epigenetic Inheritance Is Gated by Naïve Pluripotency and Dppa2. EMBO J. 2022, 41 ( 7), e108677, 10.15252/embj.2021108677
Gould, S. L.; Winter, M. J.; Norton, W. H. J.; Tyler, C. R. The Potential for Adverse Effects in Fish Exposed to Antidepressants in the Aquatic Environment. Environ. Sci. Technol. 2021, 55 ( 24), 16299- 16312, 10.1021/acs.est.1c04724
Xue, X.; Wang, R. P.; Fu, J. Modeling of Human Neurulation Using Bioengineered Pluripotent Stem Cell Culture. Current Opinion in Biomedical Engineering 2020, 127- 133, 10.1016/j.cobme.2020.02.002
Di Scipio, M.; Khan, M.; Mao, S.; Chong, M.; Judge, C.; Pathan, N.; Perrot, N.; Nelson, W.; Lali, R.; Di, S.; Morton, R.; Petch, J.; Paré, G. A Versatile, Fast and Unbiased Method for Estimation of Gene-by-Environment Interaction Effects on Biobank-Scale Datasets. Nat. Commun. 2023, 14 ( 1), 5196, 10.1038/s41467-023-40913-7
Akimova, E. T.; Breen, R.; Brazel, D. M.; Mills, M. C. Gene-Environment Dependencies Lead to Collider Bias in Models with Polygenic Scores. Sci. Rep 2021, 11 ( 1), 9457, 10.1038/s41598-021-89020-x
Huang, P.; Li, Y.; Nasser, M. I.; Guo, H.; Huang, H.; Zhao, M.; Zhu, P. Urine-Derived Induced Pluripotent Stem Cells in Cardiovascular Disease. Cardiology Research and Practice 2020, 2020, 1, 10.1155/2020/3563519
Nath, S. C.; Menendez, L.; Friedrich Ben-Nun, I. Overcoming the Variability of IPSCs in the Manufacturing of Cell-Based Therapies. Int. J. Mol. Sci. 2023, 24 ( 23), 16929, 10.3390/ijms242316929
Lee, S.; Barron, M. G. Structure-Based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists. PLoS One 2017, 12 ( 1), e0169607 10.1371/journal.pone.0169607
Wassie, A. T.; Zhao, Y.; Boyden, E. S. Expansion Microscopy: Principles and Uses in Biological Research. Nature Methods 2019, 33- 41, 10.1038/s41592-018-0219-4
Yang, L.; Li, A.; Wang, Y.; Zhang, Y. Intratumoral Microbiota: Roles in Cancer Initiation, Development and Therapeutic Efficacy. Signal Transduction and Targeted Therapy 2023, 8, 35, 10.1038/s41392-022-01304-4
Baud, A.; Casale, F. P.; Barkley-Levenson, A. M.; Farhadi, N.; Montillot, C.; Yalcin, B.; Nicod, J.; Palmer, A. A.; Stegle, O. Dissecting Indirect Genetic Effects from Peers in Laboratory Mice. Genome Biol. 2021, 22 ( 1), 216, 10.1186/s13059-021-02415-x
Kundu, K.; Tardaguila, M.; Mann, A. L.; Watt, S.; Ponstingl, H.; Vasquez, L.; Von Schiller, D.; Morrell, N. W.; Stegle, O.; Pastinen, T.; Sawcer, S. J.; Anderson, C. A.; Walter, K.; Soranzo, N. Genetic Associations at Regulatory Phenotypes Improve Fine-Mapping of Causal Variants for 12 Immune-Mediated Diseases. Nat. Genet. 2022, 54 ( 3), 251- 262, 10.1038/s41588-022-01025-y
Agrawal, N.; Lawler, K.; Davidson, C. M.; Keogh, J. M.; Legg, R.; Barroso, I.; Farooqi, I. S.; Brand, A. H. Predicting Novel Candidate Human Obesity Genes and Their Site of Action by Systematic Functional Screening in Drosophila. PLoS Biol. 2021, 19 ( 11), e3001255 10.1371/journal.pbio.3001255
Barouki, R.; Audouze, K.; Becker, C.; Blaha, L.; Coumoul, X.; Karakitsios, S.; Klanova, J.; Miller, G. W.; Price, E. J.; Sarigiannis, D. The Exposome and Toxicology: A Win-Win Collaboration. Toxicol. Sci. 2022, 186, 1- 11, 10.1093/toxsci/kfab149
Nakiwala, D.; Noyes, P. D.; Faure, P.; Chovelon, B.; Corne, C.; Gauchez, A. S.; Guergour, D.; Lyon-Caen, S.; Sakhi, A. K.; Sabaredzovic, A.; Thomsen, C.; Pin, I.; Slama, R.; Philippat, C. Phenol and Phthalate Effects on Thyroid Hormone Levels during Pregnancy: Relying on In Vitro Assays and Adverse Outcome Pathways to Inform an Epidemiological Analysis. Environ. Health Perspect 2022, 130 ( 11), 1, 10.1289/EHP10239
Mustieles, V.; D’Cruz, S. C.; Couderq, S.; Rodríguez-Carrillo, A.; Fini, J. B.; Hofer, T.; Steffensen, I. L.; Dirven, H.; Barouki, R.; Olea, N.; Fernández, M. F.; David, A. Bisphenol A and Its Analogues: A Comprehensive Review to Identify and Prioritize Effect Biomarkers for Human Biomonitoring. Environment International 2020, 144, 105811, 10.1016/j.envint.2020.105811
Caporale, N.; Leemans, M.; Birgersson, L.; Germain, P. L.; Cheroni, C.; Borbély, G.; Engdahl, E.; Lindh, C.; Bressan, R. B.; Cavallo, F.; Chorev, N. E.; D’Agostino, G. A.; Pollard, S. M.; Rigoli, M. T.; Tenderini, E.; Tobon, A. L.; Trattaro, S.; Troglio, F.; Zanella, M.; Bergman, Å.; Damdimopoulou, P.; Jönsson, M.; Kiess, W.; Kitraki, E.; Kiviranta, H.; Nånberg, E.; Öberg, M.; Rantakokko, P.; Rudén, C.; Söder, O.; Bornehag, C. G.; Demeneix, B.; Fini, J. B.; Gennings, C.; Rüegg, J.; Sturve, J.; Testa, G. From Cohorts to Molecules: Adverse Impacts of Endocrine Disrupting Mixtures. Science (1979) 2022, 375 ( 6582), 1, 10.1126/science.abe8244
Ball, N.; Bars, R.; Botham, P. A.; Cuciureanu, A.; Cronin, M. T. D.; Doe, J. E.; Dudzina, T.; Gant, T. W.; Leist, M.; van Ravenzwaay, B. A Framework for Chemical Safety Assessment Incorporating New Approach Methodologies within REACH. Arch. Toxicol. 2022, 96 ( 3), 743- 766, 10.1007/s00204-021-03215-9
Vinken, M.; Benfenati, E.; Busquet, F.; Castell, J.; Clevert, D.-A.; De Kok, T. M.; Dirven, H.; Fritsche, E.; Geris, L.; Gozalbes, R.; Hartung, T.; Jennen, D.; Jover, R.; Kandarova, H.; Kramer, N.; Krul, C.; Luechtefeld, T.; Masereeuw, R.; Roggen, E.; Schaller, S.; Vanhaecke, T.; Yang, C.; Piersma, A. H. Safer Chemicals Using Less Animals: Kick-off of the European ONTOX Project. Toxicology 2021, 458, 152846 10.1016/j.tox.2021.152846
Blum, J.; Masjosthusmann, S.; Bartmann, K.; Bendt, F.; Dolde, X.; Dönmez, A.; Förster, N.; Holzer, A. K.; Hübenthal, U.; Keßel, H. E.; Kilic, S.; Klose, J.; Pahl, M.; Stürzl, L. C.; Mangas, I.; Terron, A.; Crofton, K. M.; Scholze, M.; Mosig, A.; Leist, M.; Fritsche, E. Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals. Chemosphere 2023, 311, 137035, 10.1016/j.chemosphere.2022.137035
Bajard, L.; Adamovsky, O.; Audouze, K.; Baken, K.; Barouki, R.; Beltman, J. B.; Beronius, A.; Bonefeld-Jørgensen, E. C.; Cano-Sancho, G.; de Baat, M. L.; Di Tillio, F.; Fernández, M. F.; FitzGerald, R. E.; Gundacker, C.; Hernández, A. F.; Hilscherova, K.; Karakitsios, S.; Kuchovska, E.; Long, M.; Luijten, M.; Majid, S.; Marx-Stoelting, P.; Mustieles, V.; Negi, C. K.; Sarigiannis, D.; Scholz, S.; Sovadinova, I.; Stierum, R.; Tanabe, S.; Tollefsen, K. E.; van den Brand, A. D.; Vogs, C.; Wielsøe, M.; Wittwehr, C.; Blaha, L. Application of AOPs to Assist Regulatory Assessment of Chemical Risks - Case Studies, Needs and Recommendations. Environmental Research 2023, 217, 114650, 10.1016/j.envres.2022.114650
Marx-Stoelting, P.; Rivière, G.; Luijten, M.; Aiello-Holden, K.; Bandow, N.; Baken, K.; Cañas, A.; Castano, A.; Denys, S.; Fillol, C.; Herzler, M.; Iavicoli, I.; Karakitsios, S.; Klanova, J.; Kolossa-Gehring, M.; Koutsodimou, A.; Vicente, J. L.; Lynch, I.; Namorado, S.; Norager, S.; Pittman, A.; Rotter, S.; Sarigiannis, D.; Silva, M. J.; Theunis, J.; Tralau, T.; Uhl, M.; van Klaveren, J.; Wendt-Rasch, L.; Westerholm, E.; Rousselle, C.; Sanders, P. A Walk in the PARC: Developing and Implementing 21st Century Chemical Risk Assessment in Europe. Arch. Toxicol. 2023, 97 ( 3), 893- 908, 10.1007/s00204-022-03435-7
PrecisionTox Consortium The Precision Toxicology Initiative. Toxicol. Lett. 2023, 383, 33- 42, 10.1016/J.TOXLET.2023.05.004
Colbourne, J. K.; Shaw, J. R.; Sostare, E.; Rivetti, C.; Derelle, R.; Barnett, R.; Campos, B.; LaLone, C.; Viant, M. R.; Hodges, G. Toxicity by Descent: A Comparative Approach for Chemical Hazard Assessment. Environmental Advances 2022, 9, 100287 10.1016/j.envadv.2022.100287
Swaminathan, A.; Gliksberg, M.; Anbalagan, S.; Wigoda, N.; Levkowitz, G. Stress Resilience Is Established during Development and Is Regulated by Complement Factors. Cell Rep 2023, 42 ( 1), 111973, 10.1016/j.celrep.2022.111973
Vinken, M.; Knapen, D.; Vergauwen, L.; Hengstler, J. G.; Angrish, M.; Whelan, M. Adverse Outcome Pathways: A Concise Introduction for Toxicologists. Arch. Toxicol. 2017, 3697- 3707, 10.1007/s00204-017-2020-z
Escher, B. I.; Hackermüller, J.; Polte, T.; Scholz, S.; Aigner, A.; Altenburger, R.; Böhme, A.; Bopp, S. K.; Brack, W.; Busch, W.; Chadeau-Hyam, M.; Covaci, A.; Eisenträger, A.; Galligan, J. J.; Garcia-Reyero, N.; Hartung, T.; Hein, M.; Herberth, G.; Jahnke, A.; Kleinjans, J.; Klüver, N.; Krauss, M.; Lamoree, M.; Lehmann, I.; Luckenbach, T.; Miller, G. W.; Müller, A.; Phillips, D. H.; Reemtsma, T.; Rolle-Kampczyk, U.; Schüürmann, G.; Schwikowski, B.; Tan, Y. M.; Trump, S.; Walter-Rohde, S.; Wambaugh, J. F. From the Exposome to Mechanistic Understanding of Chemical-Induced Adverse Effects. Environ. Int. 2017, 99, 97- 106, 10.1016/j.envint.2016.11.029
Vinken, M.; Benfenati, E.; Busquet, F.; Castell, J.; Clevert, D. A.; de Kok, T. M.; Dirven, H.; Fritsche, E.; Geris, L.; Gozalbes, R.; Hartung, T.; Jennen, D.; Jover, R.; Kandarova, H.; Kramer, N.; Krul, C.; Luechtefeld, T.; Masereeuw, R.; Roggen, E.; Schaller, S.; Vanhaecke, T.; Yang, C.; Piersma, A. H. Safer Chemicals Using Less Animals: Kick-off of the European ONTOX Project. Toxicology 2021, 458, 152846, 10.1016/j.tox.2021.152846
Tan, Y.-M.; Leonard, J. A.; Edwards, S.; Teeguarden, J.; Paini, A.; Egeghy, P.; Opin, C.; Author, T. Aggregate Exposure Pathways in Support of Risk Assessment HHS Public Access Author Manuscript. Curr. Opin Toxicol 2018, 9, 8- 13, 10.1016/j.cotox.2018.03.006
European Human Exposome Network. https://www.humanexposome.eu/.
EIRENE Research Infrastructure. https://www.eirene-ri.eu/.
Wilkinson, M. D.; Dumontier, M.; Aalbersberg, Ij. J.; Appleton, G.; Axton, M.; Baak, A.; Blomberg, N.; Boiten, J. W.; da Silva Santos, L. B.; Bourne, P. E.; Bouwman, J.; Brookes, A. J.; Clark, T.; Crosas, M.; Dillo, I.; Dumon, O.; Edmunds, S.; Evelo, C. T.; Finkers, R.; Gonzalez-Beltran, A.; Gray, A. J. G.; Groth, P.; Goble, C.; Grethe, J. S.; Heringa, J.; t Hoen, P. A. C.; Hooft, R.; Kuhn, T.; Kok, R.; Kok, J.; Lusher, S. J.; Martone, M. E.; Mons, A.; Packer, A. L.; Persson, B.; Rocca-Serra, P.; Roos, M.; van Schaik, R.; Sansone, S. A.; Schultes, E.; Sengstag, T.; Slater, T.; Strawn, G.; Swertz, M. A.; Thompson, M.; Van Der Lei, J.; Van Mulligen, E.; Velterop, J.; Waagmeester, A.; Wittenburg, P.; Wolstencroft, K.; Zhao, J.; Mons, B. Comment: The FAIR Guiding Principles for Scientific Data Management and Stewardship. Sci. Data 2016, 3, 160018, 10.1038/sdata.2016.18
Pittman, M. E.; Edwards, S. W.; Ives, C.; Mortensen, H. M. AOP-DB: A Database Resource for the Exploration of Adverse Outcome Pathways through Integrated Association Networks. Toxicol. Appl. Pharmacol. 2018, 343, 71- 83, 10.1016/j.taap.2018.02.006
Global Genomic Medicine Collaborative . International HundredK+ Cohorts Consortium (IHCC).
Global Alliance for Genomics and Health . Framework for Responsible Sharing of Genomic and Health-Related Data; 2019.
